Chorioamnionitis: Practice Essentials, Background, Pathophysiology

Sections

Overview

Practice Essentials

Chorioamnionitis is a complication of pregnancy caused by bacterial infection of the fetal amnion and chorion membranes.

Signs and symptoms

The characteristic clinical signs and symptoms of chorioamnionitis include the following:

Maternal fever (intrapartum temperature >100.4°F or >37.8°C): Most frequently observed sign ^[1]
Significant maternal tachycardia (>120 beats/min)
Fetal tachycardia (>160-180 beats/min)
Purulent or foul-smelling amniotic fluid or vaginal discharge
Uterine tenderness
Maternal leukocytosis (total blood leukocyte count >15,000-18,000 cells/μL)

The risk of neonatal sepsis is increased when at least 2 of the above criteria are present. Because silent chorioamnionitis is prominent^[2]and the signs and symptoms of maternal chorioamnionitis or amniotic fluid infection are notoriously subjective, some experts recommend that, if a physician is trying to decide about an evaluation and treatment of an infant, the obstetrician should be consulted regarding whether chorioamnionitis is present.

See Clinical Presentation for more detail.

Diagnosis

Examination in pregnant women with chorioamnionitis may reveal no signs or symptoms of infection.^[2]Conversely, a pregnant woman with chorioamnionitis may appear ill, even toxic, and she may exhibit hypotension, diaphoresis, and/or cool or clammy skin.

Clinical signs and symptoms of chorioamnionitis are not always associated with placental evidence of inflammation.^[3]This is particularly true if maternal fever is the sole criterion for the diagnosis.

Examination for suspected sepsis in the neonate of a mother with chorioamnionitis often yields nonspecific and subtle findings, which may include the following:

Behavioral abnormalities (eg, lethargy, hypotonia, weak cry, poor suck)
Pulmonary: Tachypnea, respiratory distress, cyanosis, pulmonary hemorrhage, and/or apnea
Cardiovascular: Tachycardia, hypotension, prolonged capillary refill time, cool and clammy skin, pale or mottled appearance, and/or oliguria
Gastrointestinal: Abdominal distention, vomiting, diarrhea, and/or bloody stools
Central nervous system: Thermal regulatory abnormalities, behavioral abnormalities, apnea, and/or seizures
Hematologic and/or hepatic: Pallor, petechiae or purpura, and overt bleeding

Laboratory tests

During the intrapartum period, diagnosis of chorioamnionitis is usually based on clinical criteria, particularly for pregnancies at term.

Laboratory studies for asymptomatic pregnant mothers who present with premature labor or premature rupture of the membranes include the following:

Examination of amniotic fluid
Maternal blood studies
Maternal urine studies
Maternal group B streptococcal screening test

Testing in febrile pregnant women with suspected chorioamnionitis include the following:

White blood cell counts
C-reactive protein levels
Alpha1-proteinase inhibitor complex measurement
Serum interleukin-6 or ferritin levels

Studies to evaluate amniotic fluid and urogenital secretions include the following:

Bacterial cultures
Leukocyte count
Gram staining
pH
Glucose concentration
Endotoxin, lactoferrin, and/or cytokine levels
Polymerase chain reaction
Fetal fibronectin, insulinlike growth factor binding protein-1, and sialidase levels
Proteomic profiling ^[4]

The criterion standard for diagnosing early-onset bacteremia, pneumonia, or meningitis in neonates is the growth of bacteria in an appropriate specimen (ie, blood, tracheal secretions, cerebrospinal fluid). Screening tests for neonatal sepsis include white blood cell profiles and C-reactive protein determinations.

Other tests that may be used to diagnose early onset neonatal sepsis include the following:

Bacterial antigen detection in cerebrospinal fluid and/or blood
Alpha1-proteinase inhibitor complex measurement
Serum interleukin-6 or cytokine levels
Procalcitonin ^[5]

Imaging studies

Before the fetus is viable, vaginal ultrasonography can be used to identify women with a shortened cervical canal. A shortened cervical canal is associated with a higher risk of preterm delivery.^{[6, 7, 8]}

Ultrasonography may also be used to ascertain fetal well-being, utilizing the biophysical profile (BPP).

Procedures

Procedures that may be used to evaluate suspected chorioamnionitis or neonatal early onset sepsis include the following:

Needle aspiration and analysis of amniotic fluid, with ultrasonographic guidance: Can confirm the diagnosis of acute chorioamnionitis
Gross/microscopic examination of placenta, fetal membranes, umbilical cord ^[9]
CBC and inflammatory biomarkers, blood culture, and chest x-ray; lumbar puncture of neonates is controversial

See Workup for more detail.

Management

Therapy for the mother and/or neonate with chorioamnionitis includes early delivery, supportive care, and antibiotic administration.

Pharmacotherapy

Antibiotic agents used in the treatment of chorioamnionitis include the following:

Aqueous crystalline penicillin G
Clindamycin or cephalosporin: For penicillin-allergic patients
Ampicillin
Cefotaxime
Gentamicin

Nonpharmacotherapy

Supportive care of the septic neonate may include the following:

Warmth, monitoring of vital signs
Preparedness to perform a full resuscitation, including intubation, providing positive-pressure ventilation
Treatment of hypovolemia, shock, and respiratory and/or metabolic acidosis
Surfactant replacement therapy
Glucose homeostasis
Assessment and treatment of thrombocytopenia and coagulopathy, if present

Surgical option

Cesarean section may be indicated to expedite the delivery.

Although surgical intervention in the newborn is infrequently required in early onset bacterial infections of the neonate, conditions that may require such intervention include the following:

Epidural or brain abscess
Subcutaneous abscesses
Infections localized to the pleural space
Certain intra-abdominal infections (especially if intestinal perforation is present)
Bone or joint infections

See Treatment and Medication for more detail.

Background

Maternal fever during labor, and perhaps other signs and symptoms of chorioamnionitis, often results in a call to the family practitioner, pediatrician, or neonatologist related to concern for the neonate. This communication often causes an evaluation to rule out early-onset neonatal sepsis.^[10]Because of a concern for early onset sepsis (EOS) when signs and symptoms of maternal chorioamnionitis occur, 10-20 newborns are evaluated and treated with antibiotics for every infant with proven bacteremia. The reason for this clinical phenomenon is that newborns who develop EOS, defined as proven infection at < 72 hours of life, have a high mortality rate. A strong association is observed between very preterm infants dying when younger than 24 hours and chorioamnionitis.^{[11, 12]}

Heightened clinical evaluations for EOS began in the 1970s because group B streptococcal (GBS) infections resulted in a neonatal mortality of about 50%.^[13]Over the past 35 years, awareness of GBS-related neonatal morbidity and mortality have resulted in intrapartum chemoprophylaxis with antibiotics to reduce the risk of GBS disease^[14]In the presence of maternal chorioamnionitis, the dilemma for the physician is determining whether the neonate is truly at risk for localized (eg, bacterial pneumonia, meningitis) or systemic (eg, bacteremia) infection.

Early-onset bacterial infections in the newborn may occur when the mother has abnormal bacterial colonization of the urogenital tract, an ascending but silent amniotic fluid infection, or symptomatic chorioamnionitis. Thus, the physician cannot assume that maternal signs and symptoms will identify all infected infants.

GBS infections are no longer the major cause of EOS. Gram-negative bacteria are now most predominant,^[15]particularly Escherichia coli.^[16]Reports have not necessarily seen an increase in E coli -antibiotic-resistant EOS during the era of intrapartum antibiotic use.^[17]

Additionally, methicillin-resistant Staphylococcus aureus (MRSA) , already a common cause of nosocomial infection in maternity and neonatal units, looms as a potential cause of EOS.^[18]So far, maternal colonization during pregnancy with MRSA has not translated into an increase in MRSA-associated EOS, but close monitoring for this infection is warranted.^[19]

This article summarizes the history, physical examination, and laboratory findings in both mother and infant to provide appropriate decision-making tools for cost-effective management of the neonate. An entire issue of Clinics in Perinatology was devoted to infectious diseases during pregnancy.^[20]Several chapters in that monograph contain information on the pathophysiology of chorioamnionitis and its adverse consequences in the mother, fetus, and newborn. Studies have examined how inflammation and infection result in preterm birth and potential neonatal brain injury.^{[21, 22, 23]}Reilly and Faye-Petersen have also contributed a monograph on chorioamnionitis.^[9]

Pathophysiology

Abnormal bacterial colonization of the distal colon during pregnancy may create an abnormal vaginal and cervical microbial environment.^[24]More than 3 decades ago, rectovaginal colonization with GBS during pregnancy was found to be associated with GBS-related infection of the fetus or newborn.^[13]Studies have demonstrated that other types of bacteria residing in the vagina, cervix, or both ascend through intact or ruptured fetal membranes and initiate amniotic fluid infection, chorioamnionitis, or both.^[25]

Urinary tract infection during pregnancy can bathe the vagina with bacterial pathogens and is a recognized risk factor for neonatal sepsis. This observation is particularly true for untreated asymptomatic GBS-related bacteriuria.^[26]A high maternal body mass index increases the risk of EOS caused by GBS.^[27]

Bacterial vaginosis is associated with premature labor, although overt infection of the neonate with microbes causing bacterial vaginosis is uncommon. Screening for and treatment of bacterial vaginosis and other genital infections may prevent preterm birth,^[28]although Cochrane reviews conflict regarding the effectiveness of therapy.^[29]

Many associations related to infection and preterm birth have been made; however, the mechanisms of these relationships are not necessarily understood. For example, periodontitis is linked to prematurity, low birth weight, and fetal growth restriction.^[30]Blood types A and O are also associated with an increased risk for chorioamnionitis.^[31]The same researchers found relationships between alcoholism, prolonged rupture of membranes, and maternal anemia as factors related to preterm birth.^[31] Obesity during pregnancy has been related to chorioamnionitis in several reports.^{[27, 32, 33]}No association was noted between body mass index and the occurrence of maternal infectious complications when membranes ruptured before 32 weeks' gestation in one study.^[34]

In the mid trimester of pregnancy, ultrasonographic evidence of a short cervix may be the only clinical finding in intraamniotic fluid infection.^[6]Cervical insufficiency, regardless of bacterial culture results in amniotic fluid, is associated with intraamniotic inflammation, preterm birth and other adverse outcomes of pregnancy.^[35]Related issues to cervical insufficiency are mechanical methods of cervical ripening that are also suspected of increasing maternal and neonatal infections.^[36]A Cochrane review states that vaginal prostaglandin to initiate labor after premature rupture of membranes may increase maternal and fetal infection and warrants more research.^[37]Each of these factors may be associated with altered host defenses that allow ascending infection from the urogenital tract to placental tissues and amniotic fluid.^[38]

Etiology

Maternal chorioamnionitis occurs when protective mechanisms of the urogenital tract and/or uterus fail during pregnancy or when increased numbers of microbial flora or highly pathogenic microorganisms are introduced into the urogenital environment.^{[38, 39, 40, 41, 42, 43]}

Ascending infection into the vagina, then the cervix, and finally into the uterine cavity, fetal membranes, and placenta is the consequence of many factors (ie, innate host defenses, healthy bacterial flora, pathologic bacterial load, bacterial virulence factors and toxin production). A short cervix has been recognized as either a risk factor or a surrogate for microbial invasion of the amniotic fluid.^{[6, 44]}

Urogenital hygiene is obviously important in establishing healthy bacterial flora. Healthy bacteria (ie, lactobacilli)^[45] and natural peptide antibiotics in the vagina and cervix may have a role in preventing infections during pregnancy.^[46] Mucus, phagocytes, and natural antibiotic proteins (ie, lactoferrin, lysozyme, beta defensins) in the cervicovaginal secretions attempt to maintain a normal bacterial flora.^[40] Bacterial interference, mainly produced via lactobacilli living in an acidic vaginal environment and producing bacteriocins, also helps to keep pathogenic bacteria from gaining a foothold in the cervicovaginal secretions.^{[47, 48]} These mechanisms of host protection may be altered in a significant number of pregnant women who develop chorioamnionitis.

Oral hygiene may influence rectal and urogenital bacterial flora during pregnancy. Although the theory is controversial, intense interest has focused on a connection among periodontitis, abnormal rectal colonization, and preterm delivery.^{[49, 50]}

Rectal bacterial flora is believed to be important in establishing abnormal urogenital colonization during pregnancy.^{[51, 52, 53]} Alterations in vaginal and cervical host defense mechanisms during pregnancy cause vaginitis,^[54] bacterial vaginosis, urinary infections, and other urogenital infections. Orogenital contact may also alter either colonic or urogenital microbial flora and ultimately cause ascending infection and chorioamnionitis.^{[55, 56]} Similarly, coitus has been linked with chorioamnionitis.^{[57, 58]}

Currently, researchers are trying to understand how host defense mechanisms prevent urogenital infection during pregnancy. The concept of bacterial communities may be important in the pathogenesis of chorioamnionitis because certain microbes provide support to others. The prevalence and diversity of bacterial species in fetal membranes during preterm labor emphasizes further research on this topic is needed.^[59] Metagenomics uses nonculture, molecular methods to delineate all microbes inhabiting an environment. Thus, the intestinal microbiome is under intense scrutiny to understand necrotizing enterocolitis or inflammatory bowel disease. Initial reports using molecular methods to understand intrauterine infection, fetal inflammation, and preterm delivery have been published.^{[59, 60]}

Clinical events associated with chorioamnionitis include the following:

History of premature birth (with increasing risk at earlier gestational age)
Presence of premature labor
Prematurely ruptured fetal membranes (before labor has its onset)
Prolonged rupture of the fetal membranes

In a report of patients with clinical signs and symptoms of chorioamnionitis, 38% showed no histologic evidence of placental inflammation. Thus, other causes of signs and symptoms that resemble maternal chorioamnionitis must be sought.

Epidural anesthesia during labor may be associated with maternal fever and fetal tachycardia (see Special Concerns). Other conditions, such as dehydration or maternal exhaustion during labor, may result in maternal fever and must be considered as causes of the febrile state.

United States data

Incidence of maternal chorioamnionitis in the US population cannot be stated with accuracy, but the occurrence declines as pregnancy advances toward term gestation.^[9]The risk of chorioamnionitis increases based on health conditions and behaviors, as outlined in Pathophysiology. Furthermore, factors such as gestational age, economic conditions, and ethnic differences influence the incidence. Histopathology of the placenta suggests inflammation may occur in the normal course of parturition at term gestation, thus complicating the definition of chorioamnionitis. An increase in histopathologic chorioamnionitis is noted in preterm birth compared with delivery of the healthy term infant. Signs of placental inflammation are present in 42% of extremely low birth weight infants.^[61]Most agree that infection is directly or indirectly associated with 40-60% of all preterm births.^[62]

Asymptomatic infants born at term gestation to mothers who received intrapartum treatment for clinical chorioamnionitis have a 1.5% incidence rate of positive blood cultures, whereas symptomatic term infants with chorioamnionitis born to mothers who received intrapartum treatment have a 13% incidence rate of positive cultures 13%.^[63]The incidence of a positive blood culture in any full-term infant is 1 in 1250 births.^[64]Thus, intrapartum antibiotic therapy of mothers who have chorioamnionitis decreases EOS in their full-term infants.^[65]

International data

Developed countries (eg, Canada, western European countries, Australia) probably have an incidence equal to, or perhaps even less than, the rate of chorioamnionitis observed in the United States. In underdeveloped countries, premature rupture of membranes has a strong association with chorioamnionitis, and chorioamnionitis in this setting results in preterm birth with a high mortality rate.^[66]Classic studies by Naeye demonstrated that malnourished pregnant women in Africa had a higher risk of ascending urogenital infection with subsequent amniotic fluid infection.^[67]

The pathophysiology increased the risk of fetal infection and perinatal death. Infection in these malnourished women in Africa was attributed to a decrease in host defense factors in amniotic fluid that regularly prevents disease in this liquor.^[68]In developed countries where women receive suboptimal care and have poor nutrition during pregnancy, a higher incidence of infection can be expected because of altered immunedefenses.^[69]

The bacterial pathogens that cause EOS in developing countries differ from the microbes that cause disease in the United States, Canada, Europe, Australia, and other more developed countries.^{[70, 71]}For ill-defined reasons, the prevalence of GBS disease is lower in developing countries. As developing countries sustain economic development, the prevalence of different bacterial pathogens assumes a profile closer to developed countries. Information on EOS in China is beginning to appear, but the findings are akin to India, which has a lower incidence of GBS compared with Western countries. The maternal risk factors for EOS in developing countries are similar to those in developed countries.^[70]

Race-, sex-, and age-related demographics

In select populations, race may increase the risk of maternal chorioamnionitis and preterm delivery. Studying histologic chorioamnionitis and preterm birth, Holzman and others observed evidence of inflammatory pathology in 12% of placentas from white women and women of other races compared with 55% in black women.^[72] If one considers race in the context of adverse circumstances (ie, violence, human immunodeficiency virus [HIV]-infection) associated with inadequate care^{[73, 74]} or malnutrition during pregnancy,^{[75, 76]} then the incidence of placental inflammation is increased.

Gender plays an important role in neonatal infection.^{[12, 77]} Among infants with preterm birth at less than 34 weeks' gestation, prolonged rupture of the fetal membranes and male gender was a risk factor for EOS. More recent studies of EOS caused by ampicillin-resistant E coli did not find that male gender was a risk factor.^[16]

Advanced maternal age alone, defined as older than 35 years, has not been identified as a risk factor for chorioamnionitis. However, teenage pregnancy increases the risk of chorioamnionitis. Risks factors associated with teenage pregnancy and chorioamnionitis include smoking, alcohol use, anemia, unemployment, urinary tract infection, and bacterial vaginosis.^{[78, 79, 80, 81]}

Prognosis

The outcome of neonatal infections depends on the causative organism, nature of infection, time of infection onset to administration of appropriate therapy, symptoms at time of birth, and gestational age of the infant. Prematurity and birth defects are cofactors that must be considered when a prognosis is offered to parents or caregivers of an infected newborn. When each of these factors is considered, a prognosis may be provided.

Outcome may not be evident during the neonatal period, and long-term follow-up care is indicated in these infected neonates.^{[23, 82, 83, 84]}

Morbidity/mortality

Compared with neonatal deaths associated with maternal chorioamnionitis, mortality in mothers of these infants is rare. In a study of infants born at 23-32 weeks' gestation with evidence of intrauterine infection and inflammation, the neonatal death rate was 9.9-11.1%.^[85] This study is well known because the analysis concluded that administration of corticosteroids did not worsen neonatal outcome when intrauterine inflammation and infection were present.

In a debatable publication from the same study, Andrews et al concluded that in utero inflammation was not associated with an increased risk of severe adverse neurodevelopmental outcomes at age 6 years.^[19] Rather, these preterm infants born at 23-32 weeks' gestation had unfavorable outcomes because of their gestational age at birth, neonatal complications, and the IQ of the caregiver in the home after discharge. As is discussed below, other evidence refutes conclusions about chorioamnionitis and neurodevelopmental outcomes made by Andrews et al.^{[19, 23, 82, 86]}

Preterm infants born to mothers with chorioamnionitis have unfavorable neurologic outcomes. Cerebral palsy (CP) ^[87] and cognitive impairment without CP^[88] have a relationship to the presence of maternal chorioamnionitis. Functional polymorphism in the cytokine interleukin (IL)-6 gene is a risk factor for CP.^[83] In particular, funisitis and the fetal inflammatory response syndrome are related to white matter brain injury or periventricular leukomalacia that is linked to activation of cytokine networks.^[89] IL-1beta, IL-6, IL-8, IL-17, IL-18, and tumor necrosis factor (TNF)-alpha are among the cytokines identified as agents related to the fetal inflammatory response (FIR) syndrome.^{[21, 90, 91]} When extremely preterm infants have histopathologic evidence of inflammatory or infectious lesions and a severe vascular response in the placenta, the risk of CP is increased.^[92]

In addition to activation of inflammation and adverse neurologic outcomes, the risk of long-term pulmonary disease may be heightened.^{[93, 94, 95, 96]} Congenital pneumonia caused by Ureaplasma and Mycoplasma often requires longer mechanical ventilation and oxygen therapy of preterm infants and initiates a prolonged cytokine release in the neonatal lung.

More recent evidence suggests that antenatal and postnatal N-acetylcysteine (NAC) may be useful as a neuroprotective agent in the setting of maternal chorioamnionitis.^[97] In a safety study comprising 22 mothers at more than 24 weeks' gestation who presented with their 24 infants within 4 hours of being diagnosed with chorioamnionitis (follow-up, 4 years), Jenkins et al reported that newborns exposed to chorioamniotitis who received antenatal and postnatal NAC had no adverse effects, had preserved cerebrovascular regulation, and had an increased anti-inflammatory neuroprotective protein as compared to newborns who received saline treatment.^[97]

Antibiotic treatment to reduce the incidence of chronic lung disease of prematurity when the neonatal lung is colonized or infected with Ureaplasma or Mycoplasma has been disappointing. Chorioamnionitis has been linked to EOS, necrotizing enterocolitis, severe intraventricular hemorrhage in preterm infants,^[98] and spontaneous intestinal perforation.^[99]

Term infants born to mothers with chorioamnionitis have a far less chance of dying; however, the long-term morbidity in term infants is still problematic. In a reasonably homogeneous population of near-term and term infants born in the Kaiser Permanente Care Program, Wu and colleagues found chorioamnionitis, black race, advanced maternal age, and nulliparity to be independent risk factors for CP.^[100]

In preterm infants with EOS, elevated numbers of nucleated RBCs were related to increased concentrations of IL-6 in cord blood.^[101] Term infants with evidence of placental inflammation also have elevated circulating fetal nucleated RBCs, and this finding can be associated with CP.^[102]

Using amniotic fluid (AF), investigators are using proteomics and nonculture microbial identification methods, called metagenomics, to delineate all microbiota in AF and their relationship to increased intrauterine protein expression.^{[103, 104, 105]} Many proteins identified in AF are inflammatory, but unanticipated molecules are also found. These findings are associated with poor neurodevelopmental outcomes in the infants.

Complications

For the mother with chorioamnionitis, serious infectious complications include endometritis, localized pelvic infections requiring drainage, and intra-abdominal infections. Maternal chorioamnionitis or other secondary infectious complications may cause thrombosis of pelvic vessels and the potential for pulmonary emboli.

Serious complications, including septic shock, pulmonary hypertension, respiratory failure, and meningitis, occur in early onset bacterial infections of the neonate. The duration of hospitalization can be quite prolonged in an extremely premature infant because of infectious complications such as maternal chorioamnionitis or congenital pneumonia. Either condition increases the probability of chronic lung disease in prematurely born and term babies.^{[94, 106, 107]}

Patient Education

Parents or other caregivers of infected neonates need specific instructions about their subsequent care. This is particularly true for secondary complications associated with these infections. For example, caregivers of an infant with meningitis that has post-infectious hydrocephalus requiring a ventriculoperitoneal shunt placement needs to have specific instructions about shunt-related malfunction or shunt-related infection. Education of the parents related to the recognition and management of seizures would be mandatory before discharge.

Similarly, caregivers of patients with long-term pulmonary complications of congenital pneumonia may require specific education (eg, administration of oxygen or use of bronchodilators at home). Parental education in neonatal resuscitation is indicated for many graduates of the neonatal intensive care unit (NICU).

Clinical Presentation

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Michael P Sherman, MD, FAAP Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Neonatologist, Women’s and Children’s Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine

Michael P Sherman, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, American Thoracic Society, European Society for Paediatric Research, Pediatric Infectious Diseases Society, Perinatal Research Society, Society for Pediatric Research, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Naomi F Lauriello, MD Assistant Professor of Neonatology, University of Missouri Women’s and Children’s Hospital

Naomi F Lauriello, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Partner received consulting fee from Janssen Scientific Affairs for consulting; Partner received consulting fee from Reckitt Benckisser Pharmaceuticals for consulting.

Katsufumi Otsuki, MD, PhD Associate Professor, Chief, Department of Obstetrics and Gynecology, Showa University Koto-Toyosu Hospital, Japan

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Arun K Pramanik, MD, MBBS Professor of Pediatrics, Louisiana State University Health Sciences Center

Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Acknowledgements

Research by the author, Michael Sherman, is supported by NIH grant R44 HD 057744 and a grant from the Gerber Foundation. The author appreciates the review of the manuscript undertaken by Jan Sherman, RN, NNP, PhD, and her helpful recommendations for improvement.

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